Philippe Bousso Observes the Immune System in Action

Philippe Bousso uses very powerful imaging techniques to observe, in real time, the reactions of the immune system in live animals. A European Research Council (ERC) Starting Grant has made it possible for him to describe a number of mechanisms associated with processes such as those involved in cancer treatment, transplants and even skin infections.

Philippe Bousso en 2010 © Inserm/Begouen, Etienne

The ability to watch the immune system swing into action in response to infection or cancer, in real time and in vivo, is what Philippe Bousso has achieved. It all began during his post-doc at UC Berkeley (USA). A graduate of the École Polytechnique and a doctor of immunology, Bousso had the novel idea of filming immune responses in real time, in living models, in order to study them better. "Up until then, researchers could carry out in vivo observations but only after euthanizing the animal in order to retrieve the organ for study. This meant sacrificing the natural environment  when we are only too aware that cell behavior changes according to environment," explains the researcher. With the laboratory team, he then set about developing the two-photon imaging protocols that would enable real-time visualization of the immune responses in the organs of anesthetized animals.

On his return to France in 2005, the young researcher won a call for tenders enabling him to form his own team around this new observation technique, at the Institut Pasteur. Based on initial findings, he applied for ERC funding. In 2010, he was awarded a Starting Grant of almost €1.5 million for a period of five years: the purpose of his project was to study the T cells and natural killer cells involved in responses to infection and cancer. He used animal models of leishmaniasis, a disease caused by parasitic infection, in addition to other models of solid tumors and lymphoma.

Highly fruitful research and a second grant to continue

Bousso and his team then went on to describe the movements and interactions of these cells, as well as their modes of communication in these various situations. Within five years, the research had been fruitful, producing some twenty publications. This research has, for example, made it possible to:

  • discover the mode of action of an immunotherapy technique (anti-CD20) against lymphoma;
  • understand why hematopoietic stem cell grafts could lead to graft versus host disease in certain organs;
  • identify a mechanism responsible for transplant rejection; and
  • describe how cytokines propagate to control a parasitic skin infection.

But five years went by quickly and the researcher wanted to go further. In 2016, he decided to submit a new application to the ERC,  this time with the intention of provoking unnatural immune situations to observe their effects in infections and cancer. "We will manipulate immune cells at the same time as we observe them, using a combination of optogenetic and imaging techniques. Optogenetics is used to genetically modify cells in order to be able to control certain functions by exposing them to light," he specifies. "This will enable us to deepen our understanding of immune mechanisms and possibly also discover new therapeutic avenues." The ERC has just approved this second project.

"ERC grants offer a unique responsiveness making it possible to quickly recruit excellent young researchers with whom we can work for a few years. It is a real luxury! The financial guarantee they provide means that we can fully devote ourselves to the laboratory and to getting results instead of chasing other sources of funding. This offers the competitive advantage of publishing papers quickly. These grants are therefore profitable, not only for the applicants but also for young researchers. Out of my team, two have gone on to set up their own labs," explains Bousso.

Find out more about Philippe Bousso and his work

Philippe Bousso leads the Dynamics of Immune Responses team at Inserm Unit 1223/Institut Pasteur.

The immune system - Interview – 2 min 54 – video extract from series Ils font avancer la recherche SupBiotech/Institut Pasteur (2011)